Kinase inhibitors

Abstract

Compounds of formula (I) defined herein are p38 MAPK inhibitors and are useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract.

The invention claimed is: 
     
       1. A compound of formula (I) 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is H or selected from the group consisting of (C 1 -C 4 )alkyl-, (C 3 -C 7 )cycloalkyl-, (C 4 -C 7 )heterocycloalkyl-, R A O—, (R A R B )NC(O)—, R C CO(R A )N—, R A O(C 1 -C 4 )alkylene-, (R A R B )N—, R C O(O)C—, (R A R B )NSO 2 —, R C SO 2 (C 1 -C 4 )alkylene-, R C (O)CO(C 1 -C 4 )alkylene-, R C OC(O)(R A )N—, (R A R B )NCO(R D )N—, and (R A R B )N(C 1 -C 6 )alkylene-, wherein any of said alkyl, alkylene, cycloalkyl, heterocycloalkyl or heteroaryl may be optionally substituted by one or more groups selected from the group consisting of (C 1 -C 3 )alkyl, (C 3 -C 6 )cycloalkyl, 
 (C 4 -C 7 )heterocycloalkyl, —OR A , halo, and CN; 
 R 2  is H or selected from the group consisting of halo, (C 1 -C 6 )alkyl, R A O—, (R A R B )N(C 1 -C 6 )alkylene-, and R A O(C 1 -C 4 )alkylene-; 
 R A  and R B  are at each occurrence independently H or selected from the group consisting of (C 1 -C 4 )alkyl-, (C 3 -C 7 )cycloalkyl-, and (C 4 -C 7 )heterocycloalkyl-, wherein any of said alkyl, cycloalkyl, or heterocycloalkyl may be optionally substituted; 
 or R A  and R B  may form together with the nitrogen atom to which they are attached an optionally substituted 5-11-membered saturated heterocyclic monocyclic ring system optionally containing a further heteroatom which is oxygen or nitrogen; 
 R C  is selected from the group consisting of (C 1 -C 4 )alkyl-, (C 3 -C 7 )cycloalkyl-, and (C 4 -C 7 )heterocycloalkyl-, wherein any of said alkyl, cycloalkyl, or heterocycloalkyl may be optionally substituted; 
 R D  is I-1 or is selected from the group consisting of (C 1 -C 4 )alkyl-, 
 (C 3 -C 7 )cycloalkyl-, and (C 4 -C 7 )heterocycloalkyl-, wherein any of said alkyl, cycloalkyl, or heterocycloalkyl may be optionally substituted; 
 R 3  is a group of one of formula (IIa) to (IIf): 
 
       
         
           
           
               
               
           
         
         R 4  and R 5  are at each occurrence independently H or optionally substituted 
         (C 1 -C 4 )alkyl-; or R 4  and R 5  may form together with the carbon atom to which they are attached an optionally substituted 3-6-membered saturated heterocyclic monocyclic ring system; 
         R 6  and R 7  are at each occurrence independently H or optionally substituted (C 1 -C 4 )alkyl-; 
         or R 5  and R 6  may form together with the carbon or nitrogen atom to which they are attached 4-6-membered saturated heterocyclic monocyclic ring system; 
         or R 6  and R 7  may form together with the nitrogen atom to which they are attached an optionally substituted 4-6-membered saturated heterocyclic monocyclic ring system optionally containing a further heteroatom which is oxygen or nitrogen wherein said nitrogen may be optionally substituted with (C 1 -C 6 )alkyl-; 
         R 8  is H or optionally substituted (C 1 -C 4 )alkyl-; 
         X is —CH 2 , —O—, or —NR 8 ; 
         wherein “optionally substituted” means substitution by one or more groups selected from the group consisting of (C 1 -C 3 )alkyl, (C 3 -C 6 )cycloalkyl, 
         (C 4 -C 7 )heterocycloalkyl, OH, (C 1 -C 6 )alkyl-O, —NH 2 , (C 1 -C 4 )HN—, 
         (C 1 -C 4 )alkyl(C 1 -C 4 )alkyl(N)—, halo, and CN; 
         with the proviso that— 
         when R 1  is H, then R 2  is not H, halo or CH 3 ; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       2. A compound or pharmaceutically acceptable salt according to  claim 1 , which is a compound of formula (Ia) wherein a carbon stereogenic centers on the cycloalkylene portion linked to group —NH and —O— and identified, respectively, with numbers (1) and (2), have the absolute configuration shown below 
       
         
           
           
               
               
           
         
       
     
     
       3. A compound or pharmaceutically acceptable salt according to  claim 1 , wherein R 1  is H or is selected from the group consisting of (C 1 -C 4 )alkyl-, R C SO 2 —, (R A R B )NCO—, R C CO(R A )N—, R A O(C 1 -C 4 )alkylene-, (R A R B )N—, R C O(O)C—, (R A R B )NSO 2 —, R C SO 2 (C 1 -C 4 )alkylene-, R C (O)CO(C 1 -C 4 )alkylene-, and R C OC(O)(R A )N—, wherein any of said alkyl or alkylene may be optionally substituted by one or more groups —OR A ; wherein R A  and R B  are at each occurrence independently H or (C 1 -C 4 )alkyl-, which may be optionally substituted by —OH or R A  and R B  may form together with the nitrogen atom to which they are attached an optionally substituted 6 membered saturated heterocyclic monocyclic ring system optionally containing a further heteroatom which is oxygen; R C  is selected from the group consisting of (C 1 -C 4 )alkyl- and (C 3 -C 7 )cycloalkyl-, wherein any of such alkyl or cycloalkyl may be optionally substituted by one or more groups selected from the group consisting of (C 1 -C 6 )alkyl-O— and halo. 
     
     
       4. A compound or pharmaceutically acceptable salt according to  claim 1 , wherein R 2  is H or selected from the group consisting of (C 1 -C 6 )alkyl and R A O—; wherein R A  is H or (C 1 -C 4 )alkyl-. 
     
     
       5. A compound or pharmaceutically acceptable salt according to  claim 1 , wherein R 3  is a group of formula (IIb) 
       
         
           
           
               
               
           
         
         wherein R 4  and R 5  are at each occurrence independently H or (C 1 -C 4 )alkyl- optionally substituted by —OH; R 7  is H or (C 1 -C 4 )alkyl-; R 8  is H or (C 1 -C 4 )alkyl- optionally substituted by —OH. 
       
     
     
       6. A compound or pharmaceutically acceptable salt according to  claim 1 , wherein R 3  is a group of formula (IIa): 
       
         
           
           
               
               
           
         
       
       wherein R 4  and R 5  are (C 1 -C 4 )alkyl-; and R 6  and R 7  are (C 1 -C 4 )alkyl-. 
     
     
       7. A compound or pharmaceutically acceptable salt according to  claim 1 , wherein
 R 1  is H or selected from the group consisting of (C 1 -C 4 )alkyl-, R C SO 2 —, (R A R B )NC(O)—, R C CO(R A )N—, (R A R B )N—, R C O(O)C—, (R A R B )NSO 2 —, R C SO 2 (C 1 -C 4 )alkylene-, R C (O)CO(C 1 -C 4 )alkylene-, R C OC(O)(R A )N—, and (R A R B )N(C 1 -C 6 )alkylene- wherein any of said alkyl or alkylene may be optionally substituted by one or more groups —OR A ; 
 R 2  is H or selected from the group consisting of (C 1 -C 6 )alkyl-, R A O—, and R A O(C 1 -C 4 )alkylene-; 
 wherein R A  and R B  are at each occurrence independently H or (C 1 -C 4 )alkyl-, wherein any of such alkyl may be optionally substituted by 
 (C 1 -C 4 )alkyl(C 1 -C 4 )alkyl(N)—; 
 R C  is selected from the group consisting of (C 1 -C 4 )alkyl- and (C 3 -C 7 )cycloalkyl-, wherein any of such alkyl may be optionally substituted by (C 1 -C 6 )alkylO—; 
 R 3  is a group of formulae (IIa), (III)), (IIc), or (IIe) 
 
       
         
           
           
               
               
           
         
         wherein X is —CH 2 , 
         R 4  and R 5  are at each occurrence independently H or (C 1 -C 4 )alkyl-; 
         R 6  and R 7  are at each occurrence (C 1 -C 4 )alkyl-; 
         R 8  is H or (C 1 -C 4 )alkyl-. 
       
     
     
       8. A compound selected from the group consisting of
 1-(5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea hydrochloride salt; 
 1-(5-tert-butyl-3-hydroxymethyl-2-methoxy-phenyl)-3-{(1S,4R)-4-[-3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(5-tert-butyl-3-hydroxymethyl-2-methoxy-phenyl)-3-{(1S,4R)-4-[-3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea hydrochloride salt; 
 1-(5-tert-butyl-3-hydroxymethyl-2-methoxy-phenyl)-3-{(1S,4R)-4-[3-(1-dimethylamino-1-methyl-ethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea hydrochloride salt; 
 1-(5-tert-butyl-3-hydroxymethyl-2-methoxy-phenyl)-3-{(1S,4R)-4-[3-((S)-1-methyl-piperidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(5-tert-butyl-3-hydroxymethyl-2-methoxy-phenyl)-3-{(1S,4R)-4-[3-((S)-1-isopropyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 5-tert-butyl-2-methoxy-N-methyl-3-(3-{(1S,4R)-4-[-3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-benzamide hydrochloride salt; 
 N-[5-tert-butyl-3-(3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-acetamide; 
 N-[5-tert-butyl-3-(3-{(1S,4R)-4-[3-((S)-1-isopropyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-acetamide; 
 N-[5-tert-butyl-3-(3-{(1S,4R)-4-[3-(1-dimethylamino-1-methyl-ethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-acetamide; 
 N-[5-tert-butyl-2-methoxy-3-(3-{(1S,4R)-4-[3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-phenyl]-acetamide; 
 N-[5-tert-butyl-2-methoxy-3-(3-{(1S,4R)-4-[3-((S)-1-methyl-piperidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-phenyl]-acetamide; 
 1-(3-amino-5-tert-butyl-2-methoxyphenyl-3-{(1S,4R)-4-[3-(1-dimethylamino-1-methyl-ethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(3-amino-5-tert-butyl-2-methoxyphenyl-3-{(1S,4R)-4-[3-(1-dimethylamino-1-methyl-ethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(3-amino-5-tert-butyl-phenyl-3-{(1S,4R)-4-[3-(1-dimethylamino-1-methyl-ethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(3-amino-5-tert-butyl-phenyl-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 3-tert-butyl-N-methyl-5-(3-{(1S,4R)-4-[3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-benzenesulfonamide; 
 3-tert-butyl-5-(3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-N-methyl-benzenesulfonamide; 
 3-tert-butyl-5-(3-{(1S,4R)-4-[3((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-benzoic acid methyl ester; 
 3-tert-butyl-5-(3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-benzoic acid methyl ester; 
 1-(3-tert-butyl-5-methanesulfonylmethyl-phenyl)-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 acetic acid 3-tert-butyl-5-(3-{(1S,4R)-4-[3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-benzyl ester; 
 acetic acid 3-tert-butyl-5-(3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-benzyl ester; 
 N-[3-tert-butyl-5-(3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-benzyl]-methanesulfonamide; 
 [3-tert-butyl-5-(3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; 
 1-(3-tert-butyl-5-methanesulfonyl-phenyl)-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(3-tert-butyl-5-morpholin-4-yl-phenyl)-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(3-tert-butyl-5-hydroxymethyl-phenyl)-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 3-tert-butyl-N-(2-hydroxy-ethyl)-5-(3-{(1S,4R)-4-[3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-benzamide; 
 3-tert-butyl-5-(3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-N-(2-hydroxy-ethyl)-benzamide; 
 3-tert-butyl-5-(3-{(1S,4R)-4-[3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-benzamide; 
 3-tert-butyl-5-(3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-benzamide; 
 3-tert-butyl-N-methyl-5-(3-{(1S,4R)-4-[3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-benzamide; 
 3-tert-butyl-5-(3-{(1 S, 4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-N-methyl-benzamide; 
 1-(3-tert-butyl-5-morpholin-4-yl-phenyl)-3-{(1S,4R)-4-[3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(5-tert-butyl-2-hydroxymethyl-phenyl)-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(3-tert-butyl-5-piperazin-1-yl-phenyl)-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(3-tert-butyl-5-dimethylaminomethyl-phenyl)-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(3-tert-butyl-5-dimethylaminomethyl-phenyl)-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(3-tert-butyl-5-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-phenyl)-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(3-tert-butyl-5-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-phenyl)-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-[3-tert-butyl-5-(2-dimethylamino-ethoxymethyl)-phenyl]-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-[3-tert-butyl-5-(2-dimethylamino-ethoxymethyl)-phenyl]-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-[3-tert-butyl-5-(2-piperidin-1-yl-ethoxymethyl)-phenyl]-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-[3-tert-butyl-5-(2-morpholin-4-yl-ethoxymethyl)-phenyl]-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(5-tert-butyl-2-morpholin-4-ylmethyl-phenyl)-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(5-tert-butyl-2-morpholin-4-ylmethyl-phenyl)-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(3-{bis-(2-hydroxy-ethyl)-amino]-methyl}-5-tert-butyl-phenyl)-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 1-(3-{[bis-(2-hydroxy-ethyl)-amino]-methyl}-5-tert-butyl-phenyl)-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 
 or a pharmaceutically acceptable salt of said compound. 
 
     
     
       9. A pharmaceutical composition, comprising a compound or pharmaceutically acceptable salt according to  claim 1  and one or more pharmaceutically acceptable carriers. 
     
     
       10. A method of treating a disease or condition selected from the group consisting of chronic eosinophilic pneumonia, asthma, chronic obstructive pulmonary disease, adult respiratory distress syndrome, exacerbation of airways hyper-reactivity consequent to other drug therapy, or airways disease that is associated with pulmonary hypertension in a human subject, comprising administering to a subject in need thereof an effective amount a compound or pharmaceutically acceptable salt according to  claim 1 . 
     
     
       11. A method according to  claim 10 , wherein the disease or condition is chronic eosinophilic pneumonia. 
     
     
       12. A method according to  claim 10 , wherein the disease or condition is asthma. 
     
     
       13. A method according to  claim 10 , wherein the disease or condition is chronic obstructive pulmonary disease. 
     
     
       14. A method according to  claim 10 , wherein the disease or condition is adult respiratory distress syndrome. 
     
     
       15. A method according to  claim 10 , wherein the disease or condition is exacerbation of airways hyper-reactivity consequent to other drug therapy. 
     
     
       16. A method according to  claim 10 , wherein the disease or condition is airways disease that is associated with pulmonary hypertension.